Urokinase type plasminogen activator and its receptor regulate the invasive potential of gastric cancer cell lines

To assess the role of urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) on the invasive potential of cancer cells, in vitro experiments were performed using two human gastric cancer cell lines, NUGC-3 and MKN-28. NUGC-3 cells secreted a higher level of uPA than MKN-28 cells, while the uPAR expression of NUGC-3 cells was lower than that of MKN-28 cells. Both cancer cell lines expressed Met protein and did not express hepatocyte growth factor (HGF). In Matrigel invasion assay, MKN-28 cells demonstrated significantly lower invasion index than NUGC-3 cells. The addition of exogenous uPA significantly increased the invasive activity of MKN-28 cells. The uPA expression in NUGC-3 cells was enhanced by adding conditioned media of fibroblast cells or HGF. These results suggest that uPA promotes the invasive capacity of the uPAR-positive cancer cells, and that stromal cells may play an important role in cancer cell invasion by supplying uPA and/or promoting uPA production.